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1.
N Engl J Med ; 386(13): 1207-1220, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35172051

RESUMO

BACKGROUND: The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters. METHODS: We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2. RESULTS: Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 95% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously. CONCLUSIONS: Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.).


Assuntos
Imunidade Adaptativa , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Imunidade Adaptativa/imunologia , Doenças Assintomáticas , Vacina BNT162/uso terapêutico , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/prevenção & controle , Teste de Ácido Nucleico para COVID-19 , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , ChAdOx1 nCoV-19/uso terapêutico , Pessoal de Saúde , Humanos , Estudos Prospectivos , Reino Unido , Vacinação/métodos , Eficácia de Vacinas
2.
Bioinformatics ; 40(1)2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38113434

RESUMO

SUMMARY: pyCapsid is a Python package developed to facilitate the characterization of the dynamics and quasi-rigid mechanical units of protein shells and other protein complexes. The package was developed in response to the rapid increase of high-resolution structures, particularly capsids of viruses, requiring multiscale biophysical analyses. Given a protein shell, pyCapsid generates the collective vibrations of its amino-acid residues, identifies quasi-rigid mechanical regions associated with the disassembly of the structure, and maps the results back to the input proteins for interpretation. pyCapsid summarizes the main results in a report that includes publication-quality figures. AVAILABILITY AND IMPLEMENTATION: pyCapsid's source code is available under MIT License on GitHub. It is compatible with Python 3.8-3.10 and has been deployed in two leading Python package-management systems, PIP and Conda. Installation instructions and tutorials are available in the online documentation and in the pyCapsid's YouTube playlist. In addition, a cloud-based implementation of pyCapsid is available as a Google Colab notebook. pyCapsid Colab does not require installation and generates the same report and outputs as the installable version. Users can post issues regarding pyCapsid in the repository's issues section.


Assuntos
Proteínas , Software , Aminoácidos , Documentação
4.
Clin Infect Dis ; 78(6): 1443-1450, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38315893

RESUMO

BACKGROUND: People who inject drugs (PWID) are at increased risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB), but little is known about clinical outcomes of CA-SAB in PWID compared with the wider population of patients with CA-SAB. METHODS: Three national datasets were linked to provide clinical and mortality data on patients hospitalized with CA-SAB in England between 1 January 2017 and 31 December 2020. PWID were identified using the International Classification of Diseases, Tenth Revision code for "mental health and behavioral disorder due to opioid use" (F11). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for associations of PWID with 30-day all-cause mortality and 90-day hospital readmission. RESULTS: In 10 045 cases of CA-SAB, 1612 (16.0%) were PWID. Overall, 796 (7.9%) patients died within 30 days of CA-SAB admission and 1189 (11.8%) patients were readmitted to hospital within 90 days of CA-SAB. In those without infective endocarditis, there was strong evidence of lower odds of mortality among PWID compared with non-PWID (aOR, 0.47 [95% confidence interval {CI}: .33-.68]; P < .001), whereas there was no association in CA-SAB case fatality with endocarditis (aOR, 1.40 [95% CI: .87-2.25]; P = .163). PWID were less likely to be readmitted within 90 days of CA-SAB (aOR, 0.79 [95% CI: .65-.95]; P = .011). CONCLUSIONS: In this large cohort study of patients with CA-SAB in England, PWID had lower odds of death in the absence of endocarditis and lower odds of readmission within 90 days compared to non-PWID patients. This study highlights the overrepresentation of PWID among patients with CA-SAB nationally.


Assuntos
Bacteriemia , Infecções Comunitárias Adquiridas , Infecções Estafilocócicas , Staphylococcus aureus , Abuso de Substâncias por Via Intravenosa , Humanos , Masculino , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/mortalidade , Feminino , Inglaterra/epidemiologia , Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Adulto , Pessoa de Meia-Idade , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Estudos de Coortes , Readmissão do Paciente/estatística & dados numéricos , Idoso , Adulto Jovem , Fatores de Risco
5.
Lancet ; 402 Suppl 1: S93, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37997140

RESUMO

BACKGROUND: Following low incidence of invasive group A streptococcal (iGAS) infections during the COVID-19 pandemic, marked increases were noted in many countries during 2022, particularly in children. In November 2022, severe presentations of lower respiratory tract infections (LRTIs), including empyema, were notified by clinicians across the UK. UKHSA investigated this rise with the aim of informing clinical management and public health response. METHODS: We undertook a case-series analysis using multiple routine data sources, exempted from ethics approval or patient consent. We identified iGAS cases in England in children younger than 15 years with an LRTI reported between Oct 1 and Dec 21, 2022, using UKHSA laboratory surveillance data (GAS detected in LRT specimens) and notifications by clinicians and Health Protection Teams (HPTs). Symptoms, diagnoses, health-care interactions, and outcome (death or recovery) data were obtained from HPT case management notes, the National Child Mortality Database, and the NHS Digital Emergency Care Dataset. FINDINGS: We identified 147 cases of LRTI iGAS in children across England (77 [52%] male, 70 [48%] female; median age 4 years [IQR 2-6]). Predominant ethnicities were White (74 [65%] of 113 with known ethnicity) and Asian (18 [16%] of 113). Most reported symptoms were fever (90 [75%] of 120 children with ≥1 symptom) and cough (60 [50%] of 120), and 71 (48%) of all 147 children had a diagnosed respiratory viral coinfection (most commonly hMPV and RSV). 127 (86%) of children attended an emergency department, 31% (n=36/114 with onset date) at least twice within 21 days after symptom onset. 37 (25%) of 147 children died, with a median time from symptom onset to death of 4 days (IQR 3-7). Of 32 children with sample dates, 16 (84%) were tested for GAS on or after the day they died. Over half of deaths (21 [57%] of 37 deaths) occurred in the community after rapid deterioration, of whom 18 had previous contact with health-care services documented. INTERPRETATION: The UK saw an unusual rise in iGAS LRTIs in children in late 2022. One in four cases died, over half in the community. Non-specific symptoms, viral symptoms, or positive virology might have lowered suspicion of bacterial infection. Although the use of multiple available data sources expedited the analysis, varying data completeness limited interpretation. Our study highlights the need for earlier detection and identification of effective measures to prevent death. FUNDING: None.


Assuntos
Infecções Respiratórias , Infecções Estreptocócicas , Criança , Humanos , Masculino , Feminino , Pré-Escolar , Pandemias , Infecções Estreptocócicas/epidemiologia , Infecções Respiratórias/epidemiologia , Inglaterra/epidemiologia , Streptococcus pyogenes , Sistema Respiratório
6.
J Pharmacol Exp Ther ; 388(1): 201-208, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-37977812

RESUMO

Creatinine, a clinical marker for kidney function, is predominantly cleared by glomerular filtration, with active tubular secretion contributing to about 30% of its renal clearance. Recent studies suggested the potential involvement of organic anion transporter (OAT)2, in addition to the previously known organic cation transporter (OCT)2-mediated basolateral uptake, in creatinine active secretion. Here we characterized the transport mechanisms of creatinine using transfected human embryonic kidney (HEK)293 cells and freshly prepared human primary renal proximal tubule epithelial cells (hPTCs). Creatinine showed transport by OAT2 in transfected HEK293 cells. In addition, both creatinine and metformin showed transport by OCT2 and multidrug and toxin extrusion pump (MATE)1 and MATE2K, while penciclovir was selective for OAT2. Time-dependent cell accumulation was observed for creatinine and metformin in hPTCs. Their accumulation was increased by pyrimethamine but inhibited by decynium-22, likely due to differential inhibition of OCT2 versus MATEs. Additionally, indomethacin (an OAT2 inhibitor) reduced penciclovir uptake (∼75%) in hPTCs illustrating functional OAT2 activity. However, no modulation of creatinine and metformin cell accumulation was apparent with indomethacin. Creatinine transport characteristics in the presence of inhibitors approached those of metformin, an OCT2/MATE substrate, but were distinct from those of penciclovir, an OAT2-selective substrate. Moreover, indomethacin showed no significant effect on the basolateral-to-apical transport and net secretion of creatinine across hPTC monolayers. Collectively, the functional studies suggest OCT2 as the primary basolateral uptake mechanism and that OAT2 has a minimal role, in creatinine renal secretion. Our results highlight the utility of hPTCs to enable the functional assessment of renal transport mechanisms. SIGNIFICANCE STATEMENT: Our results obtained with primary hPTCs indicate that OCT2/MATE (vs. OAT2) play a major role in the active renal secretion of creatinine. Quantitative pharmacokinetic models should therefore focus on OCT2/MATE when describing serum creatinine and creatinine clearance modulation by inhibitor drugs and genotype- or disease-related activity changes. The present study highlights the utility of freshly isolated hPTCs to support solute carrier phenotyping to enable the functional assessment of renal transport mechanisms.


Assuntos
Metformina , Transportadores de Ânions Orgânicos , Humanos , Transportador 2 de Cátion Orgânico , Creatinina , Proteínas de Transporte de Cátions Orgânicos , Células HEK293 , Rim , Metformina/farmacologia , Indometacina
7.
Pharmacol Res ; 204: 107188, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705262

RESUMO

Antimicrobial resistance (AMR) poses serious challenges to the healthcare systems worldwide. Multiple factors and activities contribute to the development and spread of antimicrobial-resistant microorganisms. Monitoring progress in combating AMR is fundamental at both global and national levels to drive multisectoral actions, identify priorities, and coordinate strategies. Since 2017, the World Health Organization (WHO) has collected data through the Tracking AMR Country Self-Assessment Survey (TrACSS). TrACSS data are published in a publicly-available database. In 2023, 71 (59.9%) out of 177 responding countries reported the existence of a monitoring and evaluation plan for their National Action Plan (NAP) on AMR, and just 20 countries (11.3%) the allocation of funding to support NAP implementation. Countries reported challenges including limited financial and human resources, lack of technical capacity, and variable political commitment. Even across the Group of Seven (G7) countries, which represent some of the world's most advanced economies, many areas still need improvement, such as full implementation of infection prevention and control measures, adoption of WHO access/watch/reserve (AWaRe) classification of antibiotics, effective integration of laboratories in AMR surveillance in the animal health and food safety sectors, training and education, good manufacturing and hygiene practices in food processing, optimising pesticides use and environmental residues of antimicrobial drugs. Continuous and coordinated efforts are needed to strengthen multisectoral engagement to fight AMR.


Assuntos
Organização Mundial da Saúde , Humanos , Inquéritos e Questionários , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Autoavaliação (Psicologia) , Saúde Global , Animais
8.
Infection ; 52(4): 1469-1479, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38627354

RESUMO

PURPOSE: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality. METHODS: Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models. RESULTS: 108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time. CONCLUSION: Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy.


Assuntos
Atenção Primária à Saúde , Sepse , Humanos , Sepse/mortalidade , Sepse/epidemiologia , Idoso , Inglaterra/epidemiologia , Masculino , Feminino , Estudos de Casos e Controles , Idoso de 80 Anos ou mais , Atenção Primária à Saúde/estatística & dados numéricos , Fatores de Risco , Etnicidade/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/epidemiologia
9.
Environ Sci Technol ; 58(32): 14555-14564, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39083655

RESUMO

Existing models for estimating pesticide bioconcentration in earthworms exhibit limited applicability across different chemicals, soils and species which restricts their potential as an alternative, intermediate tier for risk assessment. We used experimental data from uptake and elimination studies using three earthworm species (Lumbricus terrestris, Aporrectodea caliginosa, Eisenia fetida), five pesticides (log Kow 1.69-6.63) and five soils (organic matter content = 0.972-39.9 wt %) to produce a first-order kinetic accumulation model. Model applicability was evaluated against a data set of 402 internal earthworm concentrations reported from the literature including chemical and soil properties outside the data range used to produce the model. Our models accurately predict body load using either porewater or bulk soil concentrations, with at least 93.5 and 84.3% of body load predictions within a factor of 10 and 5 of corresponding observed values, respectively. This suggests that there is no need to distinguish between porewater and soil exposure routes or to consider different uptake and elimination pathways when predicting earthworm bioconcentration. Our new model not only outperformed existing models in characterizing earthworm exposure to pesticides in soil, but it could also be integrated with models that account for earthworm movement and fluctuating soil pesticide concentrations due to degradation and transport.


Assuntos
Oligoquetos , Praguicidas , Poluentes do Solo , Solo , Animais , Oligoquetos/metabolismo , Praguicidas/metabolismo , Solo/química , Poluentes do Solo/metabolismo , Cinética
10.
Int J Equity Health ; 23(1): 34, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383380

RESUMO

BACKGROUND AND AIMS: Sepsis is a serious and life-threatening condition caused by a dysregulated immune response to an infection. Recent guidance issued in the UK gave recommendations around recognition and antibiotic treatment of sepsis, but did not consider factors relating to health inequalities. The aim of this study was to summarise the literature investigating associations between health inequalities and sepsis. METHODS: Searches were conducted in Embase for peer-reviewed articles published since 2010 that included sepsis in combination with one of the following five areas: socioeconomic status, race/ethnicity, community factors, medical needs and pregnancy/maternity. RESULTS: Five searches identified 1,402 studies, with 50 unique studies included in the review after screening (13 sociodemographic, 14 race/ethnicity, 3 community, 3 care/medical needs and 20 pregnancy/maternity; 3 papers examined multiple health inequalities). Most of the studies were conducted in the USA (31/50), with only four studies using UK data (all pregnancy related). Socioeconomic factors associated with increased sepsis incidence included lower socioeconomic status, unemployment and lower education level, although findings were not consistent across studies. For ethnicity, mixed results were reported. Living in a medically underserved area or being resident in a nursing home increased risk of sepsis. Mortality rates after sepsis were found to be higher in people living in rural areas or in those discharged to skilled nursing facilities while associations with ethnicity were mixed. Complications during delivery, caesarean-section delivery, increased deprivation and black and other ethnic minority race were associated with post-partum sepsis. CONCLUSION: There are clear correlations between sepsis morbidity and mortality and the presence of factors associated with health inequalities. To inform local guidance and drive public health measures, there is a need for studies conducted across more diverse setting and countries.


Assuntos
Sepse , Humanos , Fatores de Risco , Feminino , Gravidez , Fatores Socioeconômicos , Etnicidade , Desigualdades de Saúde , Disparidades nos Níveis de Saúde
11.
J Pediatr Gastroenterol Nutr ; 78(3): 534-538, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38327256

RESUMO

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.


Assuntos
Hepatite , Hepatopatias , Transplante de Fígado , Humanos , Criança , Fígado/patologia , Hepatite/patologia , Hepatopatias/patologia , Biópsia
12.
Ecotoxicol Environ Saf ; 275: 116240, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38520811

RESUMO

Modelling approaches to estimate the bioaccumulation of organic chemicals by earthworms are important for improving the realism in risk assessment of chemicals. However, the applicability of existing models is uncertain, partly due to the lack of independent datasets to test them. This study therefore conducted a comprehensive literature review on existing empirical and kinetic models that estimate the bioaccumulation of organic chemicals in earthworms and gathered two independent datasets from published literature to evaluate the predictive performance of these models. The Belfroid et al. (1995a) model is the best-performing empirical model, with 91.2% of earthworm body residue simulations within an order of magnitude of observation. However, this model is limited to the more hydrophobic pesticides and to the earthworm species Eisenia fetida or Eisenia andrei. The kinetic model proposed by Jager et al. (2003b) which out-performs that of Armitage and Gobas (2007), predicted uptake of PCB 153 in the earthworm E. andrei to within a factor of 10. However, the applicability of Jager et al.'s model to other organic compounds and other earthworm species is unknown due to the limited evaluation dataset. The model needs to be parameterised for different chemical, soil, and species types prior to use, which restricts its applicability to risk assessment on a broad scale. Both the empirical and kinetic models leave room for improvement in their ability to reliably predict bioaccumulation in earthworms. Whether they are fit for purpose in environmental risk assessment needs careful consideration on a case by case basis.


Assuntos
Oligoquetos , Praguicidas , Poluentes do Solo , Animais , Poluentes do Solo/análise , Bioacumulação , Compostos Orgânicos , Solo/química
13.
Euro Surveill ; 29(27)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967014

RESUMO

We describe an outbreak of Ralstonia pickettii in the United Kingdom, with isolates genetically indistinguishable from a 2023 Australian outbreak linked to internationally distributed saline solutions. Confirmed cases (n = 3) had bacteraemia, clinically relevant infection, indwelling venous lines and frequent healthcare contact. Multi-stakeholder intervention was required including product recall and risk communications. We recommend a low threshold for investigating clusters of Ralstonia species and similar opportunistic pathogens, considering contaminated product sources. Effective mitigation requires multi-agency partnership and international collaboration.


Assuntos
Surtos de Doenças , Infecções por Bactérias Gram-Negativas , Ralstonia pickettii , Humanos , Reino Unido/epidemiologia , Ralstonia pickettii/isolamento & purificação , Ralstonia pickettii/genética , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Solução Salina , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Austrália/epidemiologia , Contaminação de Medicamentos , Masculino
14.
Euro Surveill ; 29(32)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39119723

RESUMO

Since November 2023, the absolute number of attendances at emergency departments for pneumonia among children aged 5-14 years in England have been above expected levels for the time of year. This increased signal peaked during March 2024 but then persisted into early summer 2024 despite decreases in prevalence of seasonal respiratory pathogens. Record linkage between emergency department and laboratory databases points to this unusual activity being driven largely by Mycoplasma pneumoniae.


Assuntos
Serviço Hospitalar de Emergência , Mycoplasma pneumoniae , Pneumonia , Humanos , Criança , Inglaterra/epidemiologia , Pré-Escolar , Adolescente , Incidência , Pneumonia/epidemiologia , Masculino , Feminino , Mycoplasma pneumoniae/isolamento & purificação , Serviço Hospitalar de Emergência/estatística & dados numéricos , Prevalência , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/diagnóstico , Estações do Ano , Vigilância da População
15.
Sensors (Basel) ; 24(18)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39338630

RESUMO

The anticipated surge of Internet of Things (IoT) devices is expected to intensify the demand for mid-band spectrum resources, posing challenges to traditional spectrum sharing methods. This paper addresses the limitations of static database-assisted spectrum management frameworks and proposes a novel approach integrating high-resolution geospatial and real-time environmental data. Leveraging these inputs, the proposed framework enhances spectrum allocation accuracy, and mitigates interference more effectively, thereby increasing the access opportunities for IoT deployments. A detailed example scenario illustrates the efficacy of the proposed approach, demonstrating significant gains in spectrum sharing efficiency. It shows gains in the number of new entrants accessing the spectrum, ranging from 77% to 140%. These gains occur when moving to less conservative interference conditions and including more complex geospatial information in the propagation environment. These findings underscore the critical role of advanced spectrum sharing techniques in optimizing spectrum utilization for future IoT networks.

16.
Emerg Infect Dis ; 29(1): 184-188, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454718

RESUMO

Since June 2020, the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study has conducted routine PCR testing in UK healthcare workers and sequenced PCR-positive samples. SIREN detected increases in infections and reinfections and delected Omicron subvariant waves emergence contemporaneous with national surveillance. SIREN's sentinel surveillance methods can be used for variant surveillance.


Assuntos
COVID-19 , Humanos , Animais , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2/genética , Reino Unido/epidemiologia , Pessoal de Saúde , Reinfecção , Urodelos
17.
J Antimicrob Chemother ; 78(10): 2387-2391, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37596897

RESUMO

The plans for a new antimicrobial utilization and resistance national surveillance programme, alongside the development of quality measures and methods to monitor unintended outcomes of antimicrobial stewardship and both public and professional behaviour interventions were published in 2013. Since then, England has published an annual surveillance report including outlining progress against the ambitions of the UK national action plans on antimicrobial resistance (2013 to 2018 and 2019 to 2024). A decade later we provide a brief update on progress so far, with a focus on key highlights from the latest report published in November 2022. We also provide our recommendations for areas of focus as we move into the next decade. From an initial focus on antibiotic consumption and resistance, the report now includes surveillance data for antifungals, antivirals (including novel agents, such as those targeting SARS-CoV-2) and antimalarials. Evaluation of key stewardship interventions including professional and public engagement initiatives are also reported, as well as progress against NHS England's (NHSE's) improvement measures.


Assuntos
Anti-Infecciosos , COVID-19 , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , SARS-CoV-2 , Inglaterra/epidemiologia
18.
J Antimicrob Chemother ; 78(Suppl 2): ii37-ii42, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-37995354

RESUMO

The COVID-19 pandemic saw unprecedented resources and funds driven into research for the development, and subsequent rapid distribution, of vaccines, diagnostics and directly acting antivirals (DAAs). DAAs have undeniably prevented progression and life-threatening conditions in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are concerns of antimicrobial resistance (AMR), antiviral resistance specifically, for DAAs. To preserve activity of DAAs for COVID-19 therapy, as well as detect possible mutations conferring resistance, antimicrobial stewardship and surveillance were rapidly implemented in England. This paper expands on the ubiquitous ongoing public health activities carried out in England, including epidemiologic, virologic and genomic surveillance, to support the stewardship of DAAs and assess the deployment, safety, effectiveness and resistance potential of these novel and repurposed therapeutics.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Antibacterianos/uso terapêutico , Pandemias/prevenção & controle , Antivirais/uso terapêutico , Antivirais/farmacologia , Farmacorresistência Bacteriana , Inglaterra/epidemiologia
19.
Blood ; 137(3): 310-322, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475737

RESUMO

Platelet transfusion refractoriness results in adverse outcomes and increased health care costs. Managing refractoriness resulting from HLA alloimmunization necessitates the use of HLA antigen-matched platelets but requires a large platelet donor pool and does not guarantee full matching. We report the first randomized, double-blind, noninferiority, crossover trial comparing HLA epitope-matched (HEM) platelets with HLA standard antigen-matched (HSM) platelet transfusions. Alloimmunized, platelet-refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia were eligible. HEM platelets were selected using HLAMatchMaker epitope (specifically eplet) matching. Patients received up to 8 prophylactic HEM and HSM transfusions provided in random order. The primary outcome was 1-hour posttransfusion platelet count increment (PCI). Forty-nine patients were randomized at 14 UK hospitals. For intention to treat, numbers of evaluable transfusions were 107 and 112 for HEM and HSM methods, respectively. Unadjusted mean PCIs for HEM and HSM methods were 23.9 (standard deviation [SD], 15) and 23.5 (SD, 14.1), respectively (adjusted mean difference, -0.1; 95% confidence interval [CI], -2.9 to 2.8). Because the lower limit of the 95% CI was not greater than the predefined noninferiority limit, the HEM approach was declared noninferior to the HSM approach. There were no differences in secondary outcomes of platelet counts, transfusion requirements, and bleeding events. Adequate 1-hour PCI was more frequently observed, with a mean number of 3.2 epitope mismatches, compared with 5.5 epitope mismatches for inadequate 1-hour increments. For every additional epitope mismatch, the likelihood of an adequate PCI decreased by 15%. Epitope-matched platelets should be considered to support HLA alloimmunized patients. This trial was registered at www.isrctn.com as #ISRCTN23996532.


Assuntos
Plaquetas/imunologia , Epitopos/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Transfusão de Plaquetas , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Especificidade de Anticorpos/imunologia , Estudos Cross-Over , Epitopos/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
20.
Sex Transm Infect ; 99(8): 548-551, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37536929

RESUMO

OBJECTIVES: A global outbreak of mpox (monkeypox) has been ongoing since 2022, with most cases in the UK detected in gay, bisexual and other men who have sex with men (GBMSM). Asymptomatic and pauci-symptomatic mpox infection has been reported outside of the UK. We aimed to investigate whether mpox could be detected in specimens from GBMSM in England who were attending sexual health services (SHSs) for asymptomatic sexually transmitted infection screening. METHODS: Anonymised, residual clinical specimens from GBMSM undertaking routine asymptomatic screening for gonorrhoea (Neisseria gonorrhoeae (NG)) and chlamydia (Chlamydia trachomatis (CT)) infection were tested for the presence of mpox virus. Specimens were collected between 1 August and 7 October 2022 from three SHSs in high-mpox incidence areas in England. Testing was performed using a dual-clade, mpox virus-specific real-time PCR. RESULTS: During the collection period, 2927 clinical specimens (951 pharyngeal swabs, 1022 urine specimens and 954 rectal swabs) were obtained from 1159 GBMSM. Mpox virus was detected in four specimens from two participants who attended the same SHS at different times (the first during the week 8-12 of August, the second during the week 19-23 of September). One participant was positive in the urine specimen only, while the other tested positive at all three sites. CONCLUSIONS: A very low prevalence (2 of 1159, 0.17%) of mpox infection was detected in GBMSM attending SHS in England for asymptomatic NG/CT screening, suggesting that undetected infection in this population was unlikely to be a main driver of transmission. Confirmed mpox cases in the UK declined from over 1100 per month in June and July to 764 cumulatively during the collection period. These data give reassurance that the observed reduction in cases during the collection period was not due to undetected infection or changes in presentation among SHS attendees. Currently, there is insufficient evidence to support routine testing of asymptomatic GBMSM for mpox infection in England.


Assuntos
Infecções por Chlamydia , Gonorreia , Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Monkeypox virus , Estudos Retrospectivos , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Neisseria gonorrhoeae , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/urina , Chlamydia trachomatis , Inglaterra/epidemiologia
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